Organic chemistry 6th ed by brown, foote, iverson and anslyn 1

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Organic Chemistry, Sixth Edition
William H. Brown, Christopher
S. Foote, Brent L. Iverson, Eric V. Anslyn
Executive Editor: Lisa Lockwood
Senior Developmental Editor: Sandra Kiselica
Assistant Editor: Elizabeth Woods
Editorial Assistant: Laura Bowen

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Organic Chemistry
SIXT H EDIT ION

William H. Brown
Beloit College

Christopher S. Foote
University of California, Los Angeles

Brent L. Iverson
University of Texas, Austin

Eric V. Anslyn
University of Texas, Austin
Chapter 29 was originally contributed by

Bruce M. Novak
North Carolina State University

Australia • Brazil • Japan • Korea • Mexico • Singapore • Spain • United Kingdom • United States

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Dedication
This Sixth Edition is dedicated to the memory of our dear friend and
colleague, Christopher Foote. Chris’ insights, encouragement, and
dedication to this project can never be replaced. His kind and nurturing
spirit lives on in all who are lucky enough to have known him.

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About the Authors

WILLIAM H. BROWN is an Emeritus Professor of Chemistry at Beloit College,
where he has twice been named Teacher of the Year. His teaching responsibilities
included organic chemistry, advanced organic chemistry, and special topics in pharmacology and drug synthesis. He received his Ph.D. from Columbia University under
the direction of Gilbert Stork and did postdoctoral work at California Institute of
Technology and the University of Arizona.

CHRISTOPHER S. FOOTE received his B.S. from Yale University and his Ph.D.
from Harvard University. His scholarly credits include Sloan Fellow; Guggenheim
Fellow; ACS Baekland Award; ACS Cope Scholar; Southern California Section ACS
Tolman Medal; President, American Society for Photobiology; and Senior Editor,
Accounts of Chemical Research. He was a Professor of Chemistry at UCLA.

BRENT L. IVERSON received his B.S. from Stanford University and his Ph.D.
from the California Institute of Technology. He is a University Distinguished Teaching
Professor at The University of Texas, Austin as well as a respected researcher. Brent’s
research spans the interface of organic chemistry and molecular biology. His group

has developed several patented technologies, including an effective treatment for
anthrax.

ERIC V. ANSLYN is a University Distinguished Teaching Professor at The University of Texas at Austin. He earned his bachelor’s degree from California State
University, Northridge, his Ph.D. from the California Institute of Technology and did
postdoctoral work at Columbia University under the direction of Ronald Breslow.
Eric has won numerous teaching awards and his research focuses on the physical and
bioorganic chemistry of synthetic and natural receptors and catalysts.

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Contents in Brief
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
12.

13.
14.
15.
16.
17.
18.
19.
20.
21.
22.
23.
24.
25.
26.
27.
28.
29.

Covalent Bonding and Shapes of Molecules
Alkanes and Cycloalkanes
Stereoisomerism and Chirality
Acids and Bases
Alkenes: Bonding, Nomenclature, and Properties
Reactions of Alkenes
Alkynes
Haloalkanes, Halogenation, and Radical Reactions
Nucleophilic Substitution and b-Elimination
Alcohols
Ethers, Epoxides, and Sulfides
Infrared Spectroscopy

Nuclear Magnetic Resonance Spectroscopy
Mass Spectrometry
An Introduction to Organometallic Compounds
Aldehydes and Ketones
Carboxylic Acids
Functional Derivatives of Carboxylic Acids
Enolate Anions and Enamines
Dienes, Conjugated Systems, and Pericyclic Reactions
Benzene and the Concept of Aromaticity
Reactions of Benzene and Its Derivatives
Amines
Catalytic Carbon-Carbon Bond Formation
Carbohydrates
Lipids
Amino Acids and Proteins
Nucleic Acids
Organic Polymer Chemistry

Appendices:
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.

Thermodynamics and the Equilibrium Constant
Major Classes of Organic Acids
Bond Dissociation Enthalpies
Characteristic 1H-NMR Chemical Shifts
Characteristic 13C-NMR Chemical Shifts
Characteristic Infrared Absorption Frequencies
Electrostatic Potential Maps
Summary of Stereochemical Terms
Summary of the Rules of Nomenclature
Common Mistakes in Arrow Pushing
Organic Chemistry Road Maps

Glossary
Index
v
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Contents

Chapter 1 Covalent Bonding and Shapes of Molecules

1

1.1 Electronic Structure of Atoms 1
1.2 Lewis Model of Bonding 6
HOW TO Draw Lewis Structures from Condensed Structural Formulas

15

1.3 Functional Groups 16
1.4 Bond Angles and Shapes of Molecules 21
1.5 Polar and Nonpolar Molecules 24
CHEMICAL CONNECTIONS Fullerene—A New Form of Carbon

25

1.6 Quantum or Wave Mechanics 26
1.7 A Combined Valence Bond and Molecular Orbital Theory Approach to
Covalent Bonding

30

CONNECTIONS TO BIOLOGICAL CHEMISTRY Phosphoesters

37

1.8 Resonance 42
HOW TO Draw Curved Arrows and Push Electrons in Creating Contributing Structures

43

1.9 Molecular Orbitals for Delocalized Systems 48
1.10 Bond Lengths and Bond Strengths in Alkanes, Alkenes, and Alkynes 51
Summary 52

•

Problems 54

Chapter 2 Alkanes and Cycloalkanes

63

2.1 The Structure of Alkanes 63
2.2 Constitutional Isomerism in Alkanes 65
2.3 Nomenclature of Alkanes and the IUPAC System 67
2.4 Cycloalkanes 72
2.5 Conformations of Alkanes and Cycloalkanes 75
HOW TO Draw Alternative Chair Conformations of Cyclohexanes

86

2.6 Cis,Trans Isomerism in Cycloalkanes and Bicycloalkanes 88
HOW TO Convert Planar Cyclohexanes to Chair Cyclohexanes
CHEMICAL CONNECTIONS The Poisonous Puffer Fish

90

95

2.7 Physical Properties of Alkanes and Cycloalkanes 96
2.8 Reactions of Alkanes 99
2.9 Sources and Importance of Alkanes 101

vi
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CHEMICAL CONNECTIONS Octane Rating: What Those Numbers at the
Pump Mean
Summary 104

103
•

Problems 106

Chapter 3 Stereoisomerism and Chirality

114

3.1 Chirality—The Handedness of Molecules 114
3.2 Stereoisomerism 116
HOW TO Draw Chiral Molecules 117

3.3 Naming Chiral Centers—The R,S System 120
HOW TO Assign R or S Configuration to a Chiral Center

122

3.4 Acyclic Molecules with Two or More Stereocenters 123
3.5 Cyclic Molecules with Two or More Stereocenters 129
3.6 Tying All the Terminology Together 132
3.7 Optical Activity—How Chirality Is Detected in the Laboratory 134
3.8 The Significance of Chirality in the Biological World 137
CONNECTIONS TO BIOLOGICAL CHEMISTRY Chiral Drugs

139

CONNECTIONS TO BIOLOGICAL CHEMISTRY Amino Acids

140

3.9 Separation of Enantiomers—Resolution 140
Summary 144

•

Problems 146

Chapter 4 Acids and Bases

153

4.1 Arrhenius Acids and Bases 153
4.2 Brønsted-Lowry Acids and Bases 154
4.3 Acid Dissociation Constants, pKa, and the Relative Strengths of Acids
and Bases

160

4.4 The Position of Equilibrium in Acid-Base Reactions 162
HOW TO Calculate Equilibrium Constants for Acid-Base Reactions

163

CONNECTIONS TO BIOLOGICAL CHEMISTRY The Ionization of Functional Groups
at Physiological pH

164

4.5 Thermochemistry and Mechanisms of Acid-Base Reactions 165
4.6 Molecular Structure and Acidity 169
4.7 Lewis Acids and Bases 174
Summary 177

•

Problems 179

Chapter 5 Alkenes: Bonding, Nomenclature, and
Properties 186
5.1 Structure of Alkenes 187
HOW TO Calculate the Index of Hydrogen Deficiency

188

5.2 Nomenclature of Alkenes 190
5.3 Physical Properties of Alkenes 196
CHEMICAL CONNECTIONS The Case of the Iowa and New York Strains of the European
Corn Borer 196
Contents
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vii

5.4 Naturally Occurring Alkenes—Terpene Hydrocarbons 197
CONNECTIONS TO BIOLOGICAL CHEMISTRY The Importance of Cis Double Bonds
in Fats Versus Oils 199
Summary 200

•

Problems 201

Chapter 6 Reactions of Alkenes

206

6.1 Reactions of Alkenes—An Overview 206
6.2 Organic Reactions Involving Reactive Intermediates 207
6.3 Electrophilic Additions 217
6.4 Hydroboration-Oxidation 236
6.5 Oxidation 240
HOW TO Write a Balanced Half-Reaction

242

6.6 Reduction 244
CONNECTIONS TO BIOLOGICAL CHEMISTRY Trans Fatty Acids: What They Are
and How To Avoid Them

247

6.7 Molecules Containing Chiral Centers as Reactants
or Products

248

Summary 253

•

Problems 257

Chapter 7 Alkynes

266

7.1 Structure of Alkynes 266
7.2 Nomenclature of Alkynes 267
7.3 Physical Properties of Alkynes 269
7.4 Acidity of 1-Alkynes 269
7.5 Preparation of Alkynes 270
7.6 Electrophilic Addition to Alkynes 273
7.7 Hydration of Alkynes to Aldehydes and Ketones 275
7.8 Reduction of Alkynes 280
7.9 Organic Synthesis 282
Summary 285

•

Problems 289

Chapter 8 Haloalkanes, Halogenation, and
Radical Reactions 296
8.1 Structure 296
8.2 Nomenclature 297
8.3 Physical Properties of Haloalkanes 298
8.4 Preparation of Haloalkanes by Halogenation of Alkanes 302
8.5 Mechanism of Halogenation of Alkanes 305
CHEMICAL CONNECTIONS Freons

309

8.6 Allylic Halogenation 313
8.7 Radical Autoxidation 317
viii

Contents
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CONNECTIONS TO BIOLOGICAL CHEMISTRY Antioxidants

318

8.8 Radical Addition of HBr to Alkenes 320
Summary 323

•

Problems 326

Chapter 9 Nucleophilic Substitution and b-Elimination

331

9.1 Nucleophilic Substitution in Haloalkanes 332
9.2 Mechanisms of Nucleophilic Aliphatic Substitution 334
9.3 Experimental Evidence for SN1 and SN2 Mechanisms 338
9.4 Analysis of Several Nucleophilic Substitution Reactions 353
9.5 b-Elimination 356
9.6 Mechanisms of b-Elimination 357
9.7 Experimental Evidence for E1 and E2 Mechanisms 360
9.8 Substitution Versus Elimination 366
9.9 Analysis of Several Competitions Between Substitutions and
Eliminations

370

9.10 Neighboring Group Participation 372
CONNECTIONS TO BIOLOGICAL CHEMISTRY Mustard Gases and the Treatment
of Neoplastic Diseases
Summary 376

•

375

Problems 380

Chapter 10 Alcohols

390

10.1 Structure and Nomenclature of Alcohols 391
10.2 Physical Properties of Alcohols 393
CONNECTIONS TO BIOLOGICAL CHEMISTRY The Importance of Hydrogen Bonding
in Drug-Receptor Interactions

395

10.3 Acidity and Basicity of Alcohols 397
10.4 Reaction of Alcohols with Active Metals 398
10.5 Conversion of Alcohols to Haloalkanes and Sulfonates 399
10.6 Acid-Catalyzed Dehydration of Alcohols 405
10.7 The Pinacol Rearrangement 410
10.8 Oxidation of Alcohols 412
CHEMICAL CONNECTIONS Blood Alcohol Screening

416

CONNECTIONS TO BIOLOGICAL CHEMISTRY The Oxidation of Alcohols by NAD1 418

10.9 Thiols 420
Summary 424

•

Problems 428

Chapter 11 Ethers, Epoxides, and Sulfides

436

11.1 Structure of Ethers 436
11.2 Nomenclature of Ethers 437
11.3 Physical Properties of Ethers 438
11.4 Preparation of Ethers 439
Contents
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ix


11.5 Reactions of Ethers 443
11.6 Silyl Ethers as Protecting Groups 445
11.7 Epoxides: Structure and Nomenclature 447
11.8 Synthesis of Epoxides 448
11.9 Reactions of Epoxides 452
11.10 Ethylene Oxide and Epichlorohydrin: Building Blocks in Organic Synthesis 455
11.11 Crown Ethers 458
11.12 Sulfides 459
Summary 460

•

Problems 465

Chapter 12 Infrared Spectroscopy

474

12.1 Electromagnetic Radiation 474
12.2 Molecular Spectroscopy 475
12.3 Infrared Spectroscopy 476
12.4 Interpreting Infrared Spectra 481
12.5 Solving Infrared Spectral Problems 490
Summary 490

•

Problems 492

Chapter 13 Nuclear Magnetic Resonance
Spectroscopy 495
13.1 Nuclear Spin States 495
13.2 Orientation of Nuclear Spins in an Applied Magnetic Field 496
13.3 Nuclear Magnetic “Resonance” 498
13.4 An NMR Spectrometer 500
13.5 Equivalent Hydrogens 501
13.6 Signal Areas 503
13.7 Chemical Shift 504
13.8 Signal Splitting and the (n 1 1) Rule 508
13.9 The Origins of Signal Splitting 510
13.10 Stereochemistry and Topicity 517
CHEMICAL CONNECTIONS Magnetic Resonance Imaging

520

13

13.11 C-NMR 521
13.12 Interpretation of NMR Spectra 523
HOW TO Solve NMR Spectral Problems
Summary 528

•

526

Problems 531

Chapter 14 Mass Spectrometry

539

14.1 A Mass Spectrometer 539
14.2 Features of a Mass Spectrum 542
14.3 Interpreting Mass Spectra 546

x

Contents
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CONNECTIONS TO BIOLOGICAL CHEMISTRY Mass Spectrometry of Biological
Macromolecules

553

14.4 Mass Spectrometry in the Organic Synthesis Laboratory and
Other Applications
Summary 555

•

554

Problems 556

Chapter 15 An Introduction to Organometallic
Compounds 561
15.1 Organomagnesium and Organolithium Compounds 561
15.2 Lithium Diorganocopper (Gilman) Reagents 566
15.3 Carbenes and Carbenoids 569
Summary 573

•

Problems 575

Chapter 16 Aldehydes and Ketones

581

16.1 Structure and Bonding 581
16.2 Nomenclature 582
16.3 Physical Properties 585

16.4 Reactions 586
16.5 Addition of Carbon Nucleophiles 588
16.6 The Wittig Reaction 594
16.7 Addition of Oxygen Nucleophiles 598
16.8 Addition of Nitrogen Nucleophiles 606
CONNECTIONS TO BIOLOGICAL CHEMISTRY Pyridoxine (Vitamin B6): A Carrier
of Amino Groups

610

16.9 Keto-Enol Tautomerism 612
16.10 Oxidation 616
16.11 Reduction 617
CONNECTIONS TO BIOLOGICAL CHEMISTRY NADH: The Biological Equivalent
of a Hydride Reducing Agent

621

16.12 Reactions at an a-Carbon 624
Summary 627

•

Problems 633

Chapter 17 Carboxylic Acids

649

17.1 Structure 649

17.2 Nomenclature 650
17.3 Physical Properties 653
CHEMICAL CONNECTIONS From Willow Bark to Aspirin and Beyond

654

17.4 Acidity 655
17.5 Preparation of Carboxylic Acids 659
17.6 Reduction 659
CHEMICAL CONNECTIONS Industrial Synthesis of Acetic Acid—Transition Metal
Catalysis 660
Contents
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xi


17.7 Esterification 661
CHEMICAL CONNECTIONS The Pyrethrins: Natural Ester-containing Insecticides of
Plant Origin

663

17.8 Conversion to Acid Chlorides 664
CHEMICAL CONNECTIONS Esters as Flavoring Agents

664

17.9 Decarboxylation 665

CONNECTIONS TO BIOLOGICAL CHEMISTRY Ketone Bodies and Diabetes Mellitus 667
Summary 668

•

Problems 671

Chapter 18 Functional Derivatives of Carboxylic Acids

680

18.1 Structure and Nomenclature 681
CHEMICAL CONNECTIONS From Cocaine to Procaine and Beyond

683

CHEMICAL CONNECTIONS From Moldy Clover to a Blood Thinner

684

CHEMICAL CONNECTIONS The Penicillins and Cephalosporins: b-Lactam Antibiotics

686

18.2 Acidity of Amides, Imides, and Sulfonamides 687
CONNECTIONS TO BIOLOGICAL CHEMISTRY The Unique Structure of Amide
Bonds

688

18.3 Characteristic Reactions 689
18.4 Reaction with Water: Hydrolysis 694
HOW TO Write Mechanisms for Interconversions of Carboxylic Acid Derivatives 696
CHEMICAL CONNECTIONS Mechanistic Alternatives For Ester Hydrolysis: SN2 and
SN1 Possibilities

702

18.5 Reaction with Alcohols 708
18.6 Reactions with Ammonia and Amines 710
18.7 Reaction of Acid Chlorides with Salts of Carboxylic Acids 712
18.8 Interconversion of Functional Derivatives 712
18.9 Reactions with Organometallic Compounds 713
18.10 Reduction 716
Summary 721

•

Problems 727

Chapter 19 Enolate Anions and Enamines

742

19.1 Formation and Reactions of Enolate Anions: An Overview 742
19.2 Aldol Reaction 744
19.3 Claisen and Dieckmann Condensations 751
19.4 Claisen and Aldol Condensations in the Biological World 757
CHEMICAL CONNECTIONS Drugs That Lower Plasma Levels of Cholesterol

758

19.5 Enamines 760
19.6 Acetoacetic Ester Synthesis 763
19.7 Malonic Ester Synthesis 768
xii

Contents
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CHEMICAL CONNECTIONS Ibuprofen: The Evolution of an Industrial Synthesis

770

19.8 Conjugate Addition to a,b-Unsaturated Carbonyl
Compounds

771

19.9 Crossed Enolate Reactions Using LDA 780
Summary 784

•

Problems 790

Chapter 20 Dienes, Conjugated Systems, and Pericyclic
Reactions 810

20.1 Stability of Conjugated Dienes 810
20.2 Electrophilic Addition to Conjugated Dienes 814
20.3 UV-Visible Spectroscopy 820
20.4 Pericyclic Reaction Theory 824
CHEMICAL CONNECTIONS Curry and Cancer

825

20.5 The Diels-Alder Reaction 827
20.6 Sigmatropic Shifts 836
Summary 841

•

Problems 845

Chapter 21 Benzene and the Concept of Aromaticity

853

21.1 The Structure of Benzene 854
21.2 The Concept of Aromaticity 858
21.3 Nomenclature 867
CHEMICAL CONNECTIONS Carcinogenic Polynuclear Aromatic Hydrocarbons
and Smoking

870

21.4 Phenols 870
CHEMICAL CONNECTIONS Capsaicin, for Those Who Like It Hot

872

21.5 Reactions at a Benzylic Position 879
Summary 883

•

Problems 888

Chapter 22 Reactions of Benzene and Its Derivatives

906

22.1 Electrophilic Aromatic Substitution 907
22.2 Disubstitution and Polysubstitution 917
22.3 Nucleophilic Aromatic Substitution 924
Summary 928

•

Problems 932

Chapter 23 Amines

947

23.1 Structure and Classification 947
23.2 Nomenclature 948
23.3 Chirality of Amines and Quaternary Ammonium Ions 951

23.4 Physical Properties 952
CHEMICAL CONNECTIONS The Poison Dart Frogs of South America

953

23.5 Basicity 954
Contents
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xiii


CONNECTIONS TO BIOLOGICAL CHEMISTRY The Planarity of !NH2 Groups
on Aromatic Rings

958

23.6 Reactions with Acids 961
23.7 Preparation 964
23.8 Reaction with Nitrous Acid 966
23.9 Hofmann Elimination 974
23.10 Cope Elimination 976
Summary 977

•

Problems 983

Chapter 24 Catalytic Carbon-Carbon Bond Formation

1000

24.1 Carbon-Carbon Bond-Forming Reactions from
Earlier Chapters 1001

24.2 Organometallic Compounds and Catalysis 1002
24.3 The Heck Reaction 1002
24.4 Catalytic Allylic Alkylation 1008
24.5 Palladium-Catalyzed Cross-Coupling Reactions 1012
24.6 Alkene Metathesis 1017
Summary 1019

•

Problems 1023

Chapter 25 Carbohydrates

1037

25.1 Monosaccharides 1038
25.2 The Cyclic Structure of Monosaccharides 1042
CHEMICAL CONNECTIONS L-Ascorbic Acid (Vitamin C)

1044

25.3 Reactions of Monosaccharides 1046
CHEMICAL CONNECTIONS Testing for Glucose

1051

25.4 Disaccharides and Oligosaccharides 1052
CHEMICAL CONNECTIONS A, B, AB, and O Blood Group Substances

1055

25.5 Polysaccharides 1055
CHEMICAL CONNECTIONS High-Fructose Corn Syrup

1057

25.6 Glucosaminoglycans 1058
Summary 1059

•

Problems 1063

Chapter 26 Lipids

1071

26.1 Triglycerides 1071
26.2 Soaps and Detergents 1074
CONNECTIONS TO BIOLOGICAL CHEMISTRY FAD/FADH2: Agents for Electron
Transfer in Biological Oxidation-Reductions: Fatty Acid Oxidation

1077

26.3 Prostaglandins 1078
26.4 Steroids 1081

xiv

Contents
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26.5 Phospholipids 1085
CHEMICAL CONNECTIONS Snake Venom Phospholipases

1087

26.6 Fat-Soluble Vitamins 1088
CHEMICAL CONNECTIONS Vitamin K, Blood Clotting, and Basicity
Summary 1091

•

1090

Problems 1093

Chapter 27 Amino Acids and Proteins

1098

27.1 Amino Acids 1098

27.2 Acid-Base Properties of Amino Acids 1101
27.3 Polypeptides and Proteins 1106
27.4 Primary Structure of Polypeptides and Proteins 1107
27.5 Synthesis of Polypeptides 1113
27.6 Three-Dimensional Shapes of Polypeptides and Proteins 1117
CHEMICAL CONNECTIONS Spider Silk
Summary 1124

•

1123

Problems 1128

Chapter 28 Nucleic Acids

1134

28.1 Nucleosides and Nucleotides 1135
28.2 The Structure of DNA 1137
CHEMICAL CONNECTIONS The Search for Antiviral Drugs

1140

28.3 Ribonucleic Acids 1143
CHEMICAL CONNECTIONS The Fountain of Youth

1144

28.4 The Genetic Code 1146

28.5 Sequencing Nucleic Acids 1148
CHEMICAL CONNECTIONS DNA Fingerprinting
Summary 1153

•

1152

Problems 1155

Chapter 29 Organic Polymer Chemistry

1158

29.1 The Architecture of Polymers 1159
29.2 Polymer Notation and Nomenclature 1159
29.3 Molecular Weights of Polymers 1160
29.4 Polymer Morphology—Crystalline Versus Amorphous Materials 1161
29.5 Step-Growth Polymerizations 1162
CHEMICAL CONNECTIONS Stitches That Dissolve

1168

29.6 Chain-Growth Polymerizations 1169
CHEMICAL CONNECTIONS Organic Polymers That Conduct Electricity
CHEMICAL CONNECTIONS The Chemistry of Superglue
CHEMICAL CONNECTIONS Recycling of Plastics
Summary 1186

•

1172

1179

1184

Problems 1189

Contents
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xv


Appendices:
1. Thermodynamics and the Equilibrium Constant A-1
2. Major Classes of Organic Acids A-2
3. Bond Dissociation Enthalpies A-3
4. Characteristic 1H-NMR Chemical Shifts A-4
5. Characteristic 13C-NMR Chemical Shifts A-5
6. Characteristic Infrared Absorption Frequencies A-6
7. Electrostatic Potential Maps A-7
8. Summary of Stereochemical Terms A-8
9. Summary of the Rules of Nomenclature A-12
10. Common Mistakes in Arrow Pushing A-20
11. Organic Chemistry Road Maps A-25
Glossary G-1
Index

xvi

I-1

Contents
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List of Mechanisms

Chapter 6 Reactions of Alkenes
Electrophilic Addition of HBr to 2-Butene (Section 6.3A)
Acid-Catalyzed Hydration of Propene (Section 6.3B)
Carbocation Rearrangement in the Addition of HCl to an Alkene (Section 6.3C)
Addition of Bromine with Anti Stereoselectivity (Section 6.3D)
Halohydrin Formation and Its Anti Stereoselectivity (Section 6.3E)
Oxymercuration-Reduction of an Alkene (Section 6.3F)
Hydroboration (Section 6.4)
Oxidation of a Trialkylborane by Alkaline Hydrogen Peroxide (Section 6.4)
Formation of an Ozonide (Section 6.5B)

Chapter 7 Alkynes
Addition of HBr to an Alkyne (Section 7.6B)
HgSO4/H2SO4 Catalyzed Hydration of an Alkyne (Section 7.7B)
Reduction of an Alkyne by Sodium in Liquid Ammonia (Section 7.8C)

Chapter 8 Haloalkanes, Halogenation, and Radical Reactions
Radical Chlorination of Ethane (Section 8.5B)

Allylic Bromination of Propene Using NBS (Section 8.6A)
Radical-Initiated Non-Markovnikov Addition of HBr to Alkenes (Section 8.8)

Chapter 9 Nucleophilic Substitution and b-Elimination
An SN2 Reaction (Section 9.2A)
An SN1 Reaction (Section 9.2B)
Rearrangement During Solvolysis of 2-Chloro-3-phenylbutane (Section 9.3F)
E1 Reaction of 2-Bromo-2-methylpropane (Section 9.6A)
E2 Reaction of 2-Bromopropane (Section 9.6B)
E2 Reaction of meso-1,2-Dibromo-1,2-diphenylethane (Section 9.7C)
E2 Reaction of the Enantiomers of 1,2-Dibromo-1,2-diphenylethane (Section 9.7C)
E2 Reaction of cis-1-Chloro-2-isopropylcyclohexane (Section 9.7C)
Hydrolysis of a Sulfur Mustard—Participation by a Neighboring Group (Section 9.10)

Chapter 10 Alcohols
Reaction of a 3° Alcohol with HBr—An SN1 Reaction (Section 10.5A)
Reaction of a 1° Alcohol with HBr—An SN2 Reaction (Section 10.5A)
Rearrangement upon Treatment of Neopentyl Alcohol with HCl (Section 10.5A)
xvii
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Reaction of a Primary Alcohol with PBr3 (Section 10.5B)
Acid-Catalyzed Dehydration of 2-Butanol—An E1 Reaction (Section 10.6)
Acid-Catalyzed Dehydration of an Unbranched Primary Alcohol (Section 10.6)
The Pinacol Rearrangement of 2,3-Dimethyl-2,3-butanediol (Pinacol) (Section 10.7)
Chromic Acid Oxidation of an Alcohol (Section 10.8A)
Oxidation of a Glycol by Periodic Acid (Section 10.8C)
Oxidation of an Alcohol by NAD+ (Section 10.8C)

Chapter 11 Ethers, Epoxides, and Sulfides
Acid-Catalysed Intermolecular Dehydration of a Primary Alcohol

(Section 11.4B)

Acid-Catalyzed Addition of an Alcohol to an Alkene (Section 11.4C)
Acid-Catalyzed Cleavage of a Dialkyl Ether (Section 11.5A)
Epoxidation of an Alkene by RCO3H (Section 11.8C)
Acid-Catalyzed Hydrolysis of an Epoxide (Section 11.9A)
Nucleophilic Opening of an Epoxide Ring (Section 11.9B)

Chapter 14 Mass Spectrometry
McLafferty Rearrangement of a Ketone (Section 14.3E)
McLafferty Rearrangement of a Carboxylic Acid (Section 14.3F)

Chapter 15 An Introduction to Organometallic Compounds
Formation of Dichlorocarbene and Its Reaction with Cyclohexene

(Section 15.3B)

The Simmons-Smith Reaction with an Alkene (Section 15.3C)

Chapter 16 Aldehydes and Ketones
Grignard Reagent Reacting with Formaldehyde (Section 16.5A)
Organolithium Reagent Reacting with a Ketone (Section 16.5B)
Alkyne Anion Reacting with a Ketone (Section 16.5C)
Formation of a Cyanohydrin (Section 16.5D)
The Wittig Reaction (Section 16.6)
Base-Catalyzed Formation of a Hemiacetal (Section 16.7B)

Acid-Catalyzed Formation of a Hemiacetal (Section 16.7B)
Acid-Catalyzed Formation of an Acetal (Section 16.7B)
Formation of an Imine from an Aldehyde or Ketone (Section 16.8A)
Base-Catalyzed Equilibration of Keto and Enol Tautomers (Section 16.9)
Acid-Catalyzed Equilibration of Keto and Enol Tautomers (Section 16.9A)
Sodium Borohydride Reduction of an Aldehyde or Ketone (Section 16.11A)
Wolff-Kishner Reduction (Section 16.11E)
Acid-Catalyzed a-Halogenation of a Ketone (Section 16.12C)
Base-Promoted a-Halogenation of a Ketone (Section 16.12C)

xviii

List of Mechanisms
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Chapter 17 Carboxylic Acids
Formation of a Methyl Ester Using Diazomethane (Section 17.7B)
Decarboxylation of a b-Ketocarboxylic Acid (Section 17.9A)
Decarboxylation of a b-Dicarboxylic Acid (Section 17.9B)

Chapter 18 Functional Derivatives of Carboxylic Acids
Fischer Esterification (Section 18.3E)
Hydrolysis of an Acid Chloride (Section 18.4A)
Hydrolysis of an Ester in Aqueous Base (Saponification) (Section 18.4C)
Hydrolysis of an Amide in Aqueous Acid (Section 18.4D)
Hydrolysis of an Amide in Aqueous Base (Section 18.4D)
Hydrolysis of a Cyano Group to an Amide in Aqueous Base (Section 18.4E)
Reaction of an Acid Chloride and Ammonia (Section 18.6A)

Reaction of an Ester with a Grignard Reagent (Section 18.9A)
Reduction of an Ester by Lithium Aluminum Hydride (Section 18.10A)
Reduction of an Amide by Lithium Aluminum Hydride (Section 18.10B)

Chapter 19 Enolate Anions and Enamines
Base-Catalyzed Aldol Reaction (Section 19.2A)
Acid-Catalyzed Aldol Reaction (Section 19.2A)
Acid-Catalyzed Dehydration of an Aldol Product (Section 19.2A)
Claisen Condensation (Section 19.3A)
Alkylation of an Enamine (Section 19.5A)
Michael Reaction—Conjugate Addition of Enolate Anions (Section 19.8A)

Chapter 20 Dienes, Conjugated Systems, and
Pericylic Reactions
1,2- and 1,4-Addition to a Conjugated Diene (Section 20.2A)
The Claisen Rearrangement (Section 20.6A)
The Cope Rearrangement (Section 20.6B)

Chapter 21 Benzene and the Concept of Aromaticity
Kolbe Carboxylation of Phenol (Section 21.4E)

Chapter 22 Reactions of Benzene and its Derivatives
Electrophilic Aromatic Substitution—Chlorination (Section 22.1A)
Formation of the Nitronium Ion (Section 22.1B)
Friedel-Crafts Alkylation (Section 22.1C)
Friedel-Crafts Acylation—Generation of an Acylium Ion (Section 22.1C)
Nucleophilic Aromatic Substitution via a Benzyne Intermediate

(Section 22.3A)

Nucleophilic Aromatic Substitution by Addition-Elimination (Section 22.3B)

List of Mechanisms
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xix


Chapter 23 Amines
Formation of the Nitrosyl Cation (Section 23.8)
Reaction of a 2° Amine with the Nitrosyl Cation to Give an N-Nitrosamine
(Section 23.8C)

Reaction of a 1° Amine with Nitrous Acid (Section 23.8D)
The Tiffeneau-Demjanov Reaction (Section 23.8D)
The Hofmann Elimination (Section 23.9)
The Cope Elimination (Section 23.10)

Chapter 24 Catalytic Carbon-Carbon Bond Formation
The Heck Reaction (Section 24.3B)
The Catalytic Cycle for Allylic Alkylation (Section 24.4A)
The Catalytic Cycle of Cross-Coupling (Section 24.4A)

Chapter 26 Lipids
Oxidation of a Fatty Acid !CH2!CH2! to !CH"CH! by FAD (Section 26.2C)

Chapter 27 Amino Acids and Proteins
Cleavage of a Peptide Bond at Methionine by Cyanogen Bromide

(Section 27.4B)

Edman Degradation—Cleavage of an N-Terminal Amino Acid (Section 27.4B)

Chapter 29 Organic Polymer Chemistry
Radical Polymerization of a Substituted Ethylene (Section 29.6A)
Ziegler-Natta Catalysis of Ethylene Polymerization (Section 29.6B)
Homogeneous Catalysis for Ziegler-Natta Coordination Polymerization (Section 29.6B)
Initiation of Anionic Polymerization of Alkenes (Section 29.6D)
Initiation of Anionic Polymerization of Butadiene (Section 29.6D)
Initiation of Cationic Polymerization of an Alkene by HF ? BF3 (Section 29.6D)
Initiation of Cationic Polymerization of an Alkene by a Lewis Acid

xx

(Section 29.6D)

List of Mechanisms
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Preface

Introduction
This Sixth Edition of Organic Chemistry significantly extends the transformation
started in the Fifth Edition. Students taking an organic chemistry course have two
objectives; the first is to learn organic chemistry, and the second is to establish the
intellectual foundation for other molecular science courses. Most often, these other
courses involve biochemistry or specialized topics such as materials science. This

textbook addresses these two objectives head-on by first presenting mechanistic and
synthetic organic chemistry geared toward giving students a fundamental understanding of organic molecules and reactions, as well as their mechanisms and uses
in organic synthesis. The text then builds upon the fundamentals by providing
an emphasis on bridging concepts that will prepare students for subsequent
science courses. Several unique elements including comprehensive end of chapter
summaries, a new paradigm for learning mechanisms and a new learning tool we
call Organic Chemistry Road Maps have been included to increase the efficiency of
student studying and learning.

Making Connections
All the important reaction mechanistic and synthetic details are still found throughout
the text, but we have increased the important connections between different reaction
mechanisms. The intent is to make the study of organic chemistry a process involving
the learning and application of fundamental principles and not an exercise in
memorization. Throughout this edition, the uniting concept of nucleophiles reacting
with electrophiles is highlighted. Especially helpful is the use of electrostatic potential
surface models of reacting molecules. These maps emphasize, in an easily interpreted,
color-coded fashion, how the majority of reactions involve areas of higher electron
density on one reactant (a nucleophile) interacting with areas of lower electron
density on the other reactant (an electrophile).

A Fresh Look at Mechanisms
Starting in Chapter 6, this edition introduces a revolutionary new paradigm for learning organic chemistry mechanisms. Students are introduced to a small set of individual
mechanism elements in Chapter 6. The mechanism elements are explained in detail,
including when they are appropriate to use. Reaction mechanisms throughout the
book are then described as combinations of these individual mechanism elements,
which are written in stepwise fashion. This new approach not only simplifies the learning
of mechanisms for students, it makes it easier for them to recognize similarities
and differences among related reactions. Most important, it makes the prediction
of reaction mechanisms simpler, analogous to a multiple choice situation in which

the correct mechanism element is chosen from a small menu of choices. Also, to
give students more confidence with writing mechanisms, Appendix 10 on Common
Mistakes in Arrow Pushing has been added. In addition, many mechanisms (particularly
in Chapter 18) have been broken down into more descriptive steps to make it easier
for students to understand the concepts involved.
xxi
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